Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists
The design, synthesis and structure-activity relationship studies of some novel trisubstituted pyrimidine amide derivatives prepared as CCR4 antagonists are described. The activities of these compounds were evaluated by the CCR4-MDC chemotaxis inhibition assay. Compound 1, which we have previously r...
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doaj-a0275585939f4778b255f39fb7db20552020-11-24T22:57:22ZengMDPI AGMolecules1420-30492014-03-011933539355110.3390/molecules19033539molecules19033539Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 AntagonistsLibao Xu0Yang Zhang1Wenjie Dai2Ying Wang3Dan Jiang4Lili Wang5Junhai Xiao6Xiaohong Yang7Song Li8School of Pharmaceutical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Science Center, Beijing 100191, ChinaShenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, ChinaDepartment of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Science Center, Beijing 100191, ChinaLaboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology & Toxicology, Beijing 100850, ChinaLaboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology & Toxicology, Beijing 100850, ChinaLaboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology & Toxicology, Beijing 100850, ChinaSchool of Pharmaceutical Sciences, Jilin University, Changchun 130021, ChinaSchool of Pharmaceutical Sciences, Jilin University, Changchun 130021, ChinaThe design, synthesis and structure-activity relationship studies of some novel trisubstituted pyrimidine amide derivatives prepared as CCR4 antagonists are described. The activities of these compounds were evaluated by the CCR4-MDC chemotaxis inhibition assay. Compound 1, which we have previously reported as a potent antagonist of CCR4, was employed as the positive control. The results indicated that most of the synthesized compounds exhibited some chemotaxis inhibition activity against CCR4. Of these new compounds, compounds 6c, 12a and 12b, with IC50 values of 0.064, 0.077 and 0.069 μM, respectively, showed higher or similar activity compared with compound 1 (IC50 of 0.078 μM). These compounds provide a basis for further structural modifications. The systematic structure-activity relationship of these trisubstituted pyrimidine amide derivatives was discussed based on the obtained experimental data. The results from the SAR study may be useful for identifying more potent CCR4 antagonists.http://www.mdpi.com/1420-3049/19/3/3539antagonistspyrimidine amidessynthesisstructure-activity relationship |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Libao Xu Yang Zhang Wenjie Dai Ying Wang Dan Jiang Lili Wang Junhai Xiao Xiaohong Yang Song Li |
spellingShingle |
Libao Xu Yang Zhang Wenjie Dai Ying Wang Dan Jiang Lili Wang Junhai Xiao Xiaohong Yang Song Li Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists Molecules antagonists pyrimidine amides synthesis structure-activity relationship |
author_facet |
Libao Xu Yang Zhang Wenjie Dai Ying Wang Dan Jiang Lili Wang Junhai Xiao Xiaohong Yang Song Li |
author_sort |
Libao Xu |
title |
Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists |
title_short |
Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists |
title_full |
Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists |
title_fullStr |
Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists |
title_full_unstemmed |
Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists |
title_sort |
design, synthesis and sar study of novel trisubstituted pyrimidine amide derivatives as ccr4 antagonists |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2014-03-01 |
description |
The design, synthesis and structure-activity relationship studies of some novel trisubstituted pyrimidine amide derivatives prepared as CCR4 antagonists are described. The activities of these compounds were evaluated by the CCR4-MDC chemotaxis inhibition assay. Compound 1, which we have previously reported as a potent antagonist of CCR4, was employed as the positive control. The results indicated that most of the synthesized compounds exhibited some chemotaxis inhibition activity against CCR4. Of these new compounds, compounds 6c, 12a and 12b, with IC50 values of 0.064, 0.077 and 0.069 μM, respectively, showed higher or similar activity compared with compound 1 (IC50 of 0.078 μM). These compounds provide a basis for further structural modifications. The systematic structure-activity relationship of these trisubstituted pyrimidine amide derivatives was discussed based on the obtained experimental data. The results from the SAR study may be useful for identifying more potent CCR4 antagonists. |
topic |
antagonists pyrimidine amides synthesis structure-activity relationship |
url |
http://www.mdpi.com/1420-3049/19/3/3539 |
work_keys_str_mv |
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